: The specific goals of the current proposal are to: (1) examine the contributions of working memory (rehearsal maintenance), focused and divided attention, and motivational factors to the recent memory deficits of MS patients, (2) determine if quantitative measurements of MR relaxation parameters (T1, T2 and proton density) are effective in predicting cognitive and affective disturbance, particularly when compared to quantitative MRI indices of lesion area and location, ventricular size, and size of the corpus callosum, (3) study the long-term changes in cognition, affect, neurological status, and neuroimaging of a large, representative sample of MS patients using a prospective, longitudinal research design, and (4) investigate the long-term, neuropsychological significance of leuko-araiosis in otherwise healthy individual using a prospective, longitudinal design. By the end of the proposed project, 100 MS patients and 100 demographically-matched, healthy controls will have undergone three 2-day outpatient evaluations separated by 3 year retest intervals. At each evaluation, subjects will be administered a comprehensive battery of cognitive and affective psychometric tests, and will undergo a neurologic examination (including measures of disability), MRI, an audiological examination, a videotaped psychosocial interview, and an in-home evaluation of activities of daily living.